Platelets are essentially involved in promoting the interactions and activations of coagulation proteins in the contact phase of intrinsic coagulation. Additionally, platelets enhance the activation of prothrombin by factor Xa several hundred thousand fold compared with factor Xa alone. A number of lines of evidence suggest the possibility of a platelet role in activation of factor IX: 1) Human platelets participate in the activation of factor X by an enzymatic complex including factors IXa and VIII, probably assembled on platelet membranes; 2) platelets have a factor XI activity and antigen which resides in the plasma membrane and participates in contact activation reactions; 3) platelets participate in the proteolytic activation of factor XI, even in the absence of added HMW kininogen and factor XII; and 4) the activities of purified or plasma factor XI are enhanced 10-40-fold in clotting assays in the presence of platelets. The development of a new technique for labelling the activation peptide of factor IX and measuring its release during proteolytic activation of the molecule will provide a highly specific, simple and quantitative method for examining the activation of factor IX. This technique and a variety of other assay procedures will be employed to investigate: 1) The interaction of factors IX and IXa with platelets; 2) platelet influence on factor IX activation by factor XIa, and 3) platelet involvement in factor IXa activation of factor X. The advantages of this approach are: 1) the specific reactions to be studied can be isolated; 2) these reactions can be studied both in purified systems and in plasma and the results compared; 3) the need for other surfaces, such as kaolin, which activates platelets as well as contact proteins can be eliminated or controlled; and 4) kinetic parameters can be derived and their biological relevance examined.